JP2005522461A - エポチロン誘導体およびアルキル化剤を含む組合せ剤 - Google Patents

エポチロン誘導体およびアルキル化剤を含む組合せ剤 Download PDF

Info

Publication number: JP2005522461A
Authority: JP; Japan
Prior art keywords: combination; combination according; pharmaceutically acceptable; formula; present
Prior art date: 2002-03-08
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

JP2003574174A

Other languages

English (en)

Japanese (ja)

Inventor

ジュディス・ローズ・アンダーソン

ジョン・デイビッド・ロサーメル

ポール・エム・ジェイ・マクシーヒー

アラン・ボディ

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Newcastle University of Upon Tyne

Original Assignee

Newcastle University of Upon Tyne

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-03-08

Filing date

2003-03-07

Publication date

2005-07-28

2003-03-07 Application filed by Newcastle University of Upon Tyne filed Critical Newcastle University of Upon Tyne

2005-07-28 Publication of JP2005522461A publication Critical patent/JP2005522461A/ja

Status Withdrawn legal-status Critical Current

Links

150000003883 epothilone derivatives Chemical class 0.000 title claims abstract description 13
229940100198 alkylating agent Drugs 0.000 title claims abstract description 12
239000002168 alkylating agent Substances 0.000 title claims abstract description 12
206010028980 Neoplasm Diseases 0.000 claims abstract description 27
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
238000011282 treatment Methods 0.000 claims abstract description 21
201000010099 disease Diseases 0.000 claims abstract description 18
239000001257 hydrogen Substances 0.000 claims abstract description 17
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
230000002062 proliferating effect Effects 0.000 claims abstract description 17
125000000217 alkyl group Chemical group 0.000 claims abstract description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
150000001875 compounds Chemical class 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 17
229960001842 estramustine Drugs 0.000 claims description 16
FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 claims description 16
239000004480 active ingredient Substances 0.000 claims description 15
238000000034 method Methods 0.000 claims description 11
241001465754 Metazoa Species 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 6
239000003795 chemical substances by application Substances 0.000 claims description 5
-1 ethyleneimines Chemical class 0.000 claims description 5
CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical class CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 claims description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
150000008052 alkyl sulfonates Chemical class 0.000 claims description 4
TWVFRCAHAAGDNR-UHFFFAOYSA-N imidazo[4,5-e]tetrazin-6-one Chemical class N1=NN=NC2=NC(=O)N=C21 TWVFRCAHAAGDNR-UHFFFAOYSA-N 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
229940045714 alkyl sulfonate alkylating agent Drugs 0.000 claims description 3
230000015572 biosynthetic process Effects 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
150000002118 epoxides Chemical class 0.000 claims description 3
MQXVYODZCMMZEM-ZYUZMQFOSA-N mannomustine Chemical compound ClCCNC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CNCCCl MQXVYODZCMMZEM-ZYUZMQFOSA-N 0.000 claims description 3
229950008612 mannomustine Drugs 0.000 claims description 3
206010027476 Metastases Diseases 0.000 claims description 2
229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 claims description 2
150000001541 aziridines Chemical class 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims description 2
230000009401 metastasis Effects 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
229940045713 antineoplastic alkylating drug ethylene imines Drugs 0.000 claims 1
239000000126 substance Substances 0.000 abstract 1
230000000694 effects Effects 0.000 description 16
239000008194 pharmaceutical composition Substances 0.000 description 8
238000012360 testing method Methods 0.000 description 7
BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 6
HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 6
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical class C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 5
QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 5
229960004961 mechlorethamine Drugs 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
229960004964 temozolomide Drugs 0.000 description 5
230000037396 body weight Effects 0.000 description 4
238000001802 infusion Methods 0.000 description 4
HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
238000009097 single-agent therapy Methods 0.000 description 4
230000003442 weekly effect Effects 0.000 description 4
206010061818 Disease progression Diseases 0.000 description 3
230000009286 beneficial effect Effects 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
230000002195 synergetic effect Effects 0.000 description 3
FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 2
102000029749 Microtubule Human genes 0.000 description 2
108091022875 Microtubule Proteins 0.000 description 2
VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 2
206010060862 Prostate cancer Diseases 0.000 description 2
208000000236 Prostatic Neoplasms Diseases 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
230000009471 action Effects 0.000 description 2
230000001028 anti-proliverative effect Effects 0.000 description 2
230000008901 benefit Effects 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
229960003901 dacarbazine Drugs 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
230000005750 disease progression Effects 0.000 description 2
229940079593 drug Drugs 0.000 description 2
229930013356 epothilone Natural products 0.000 description 2
230000012010 growth Effects 0.000 description 2
150000003951 lactams Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
210000004688 microtubule Anatomy 0.000 description 2
229960005485 mitobronitol Drugs 0.000 description 2
239000000203 mixture Substances 0.000 description 2
OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 description 2
229960000952 pipobroman Drugs 0.000 description 2
239000000902 placebo Substances 0.000 description 2
229940068196 placebo Drugs 0.000 description 2
CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 2
229960000624 procarbazine Drugs 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
VNBAOSVONFJBKP-UHFFFAOYSA-N 2-chloro-n,n-bis(2-chloroethyl)propan-1-amine;hydrochloride Chemical compound Cl.CC(Cl)CN(CCCl)CCCl VNBAOSVONFJBKP-UHFFFAOYSA-N 0.000 description 1
IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
235000003351 Brassica cretica Nutrition 0.000 description 1
235000003343 Brassica rupestris Nutrition 0.000 description 1
241000219193 Brassicaceae Species 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
206010008342 Cervix carcinoma Diseases 0.000 description 1
MKQWTWSXVILIKJ-LXGUWJNJSA-N Chlorozotocin Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](C=O)NC(=O)N(N=O)CCCl MKQWTWSXVILIKJ-LXGUWJNJSA-N 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
BEFZAMRWPCMWFJ-JRBBLYSQSA-N Epothilone C Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C=C\C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C BEFZAMRWPCMWFJ-JRBBLYSQSA-N 0.000 description 1
XOZIUKBZLSUILX-SDMHVBBESA-N Epothilone D Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C(/C)=C/C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C XOZIUKBZLSUILX-SDMHVBBESA-N 0.000 description 1
108700012941 GNRH1 Proteins 0.000 description 1
206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
208000007766 Kaposi sarcoma Diseases 0.000 description 1
GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
229930012538 Paclitaxel Natural products 0.000 description 1
HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
AHHFEZNOXOZZQA-ZEBDFXRSSA-N Ranimustine Chemical compound CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O AHHFEZNOXOZZQA-ZEBDFXRSSA-N 0.000 description 1
206010041067 Small cell lung cancer Diseases 0.000 description 1
229940123237 Taxane Drugs 0.000 description 1
FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
FYAMXEPQQLNQDM-UHFFFAOYSA-N Tris(1-aziridinyl)phosphine oxide Chemical compound C1CN1P(N1CC1)(=O)N1CC1 FYAMXEPQQLNQDM-UHFFFAOYSA-N 0.000 description 1
102000004243 Tubulin Human genes 0.000 description 1
108090000704 Tubulin Proteins 0.000 description 1
208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
SPJCRMJCFSJKDE-ZWBUGVOYSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] 2-[4-[bis(2-chloroethyl)amino]phenyl]acetate Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)C(=O)CC1=CC=C(N(CCCl)CCCl)C=C1 SPJCRMJCFSJKDE-ZWBUGVOYSA-N 0.000 description 1
VSXWQPUJZFSQLV-WAJSLEGFSA-N [N].OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)O)[C@@H]4[C@@H]3CCC2=C1 Chemical compound [N].OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)O)[C@@H]4[C@@H]3CCC2=C1 VSXWQPUJZFSQLV-WAJSLEGFSA-N 0.000 description 1
USDJGQLNFPZEON-UHFFFAOYSA-N [[4,6-bis(hydroxymethylamino)-1,3,5-triazin-2-yl]amino]methanol Chemical compound OCNC1=NC(NCO)=NC(NCO)=N1 USDJGQLNFPZEON-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
239000000556 agonist Substances 0.000 description 1
229960000473 altretamine Drugs 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
230000033115 angiogenesis Effects 0.000 description 1
230000003474 anti-emetic effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000002111 antiemetic agent Substances 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
229950005567 benzodepa Drugs 0.000 description 1
VFIUCBTYGKMLCM-UHFFFAOYSA-N benzyl n-[bis(aziridin-1-yl)phosphoryl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NP(=O)(N1CC1)N1CC1 VFIUCBTYGKMLCM-UHFFFAOYSA-N 0.000 description 1
208000036815 beta tubulin Diseases 0.000 description 1
230000002146 bilateral effect Effects 0.000 description 1
229960002092 busulfan Drugs 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
235000013877 carbamide Nutrition 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
229960005243 carmustine Drugs 0.000 description 1
239000000969 carrier Substances 0.000 description 1
201000010881 cervical cancer Diseases 0.000 description 1
229960004630 chlorambucil Drugs 0.000 description 1
JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
229960001480 chlorozotocin Drugs 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
238000000315 cryotherapy Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
230000002074 deregulated effect Effects 0.000 description 1
BEFZAMRWPCMWFJ-UHFFFAOYSA-N desoxyepothilone A Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC=CCC1C(C)=CC1=CSC(C)=N1 BEFZAMRWPCMWFJ-UHFFFAOYSA-N 0.000 description 1
XOZIUKBZLSUILX-UHFFFAOYSA-N desoxyepothilone B Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC(C)=CCC1C(C)=CC1=CSC(C)=N1 XOZIUKBZLSUILX-UHFFFAOYSA-N 0.000 description 1
238000011161 development Methods 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000008298 dragée Substances 0.000 description 1
230000002888 effect on disease Effects 0.000 description 1
229940000733 emcyt Drugs 0.000 description 1
HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical compound C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 1
BEFZAMRWPCMWFJ-QJKGZULSSA-N epothilone C Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 BEFZAMRWPCMWFJ-QJKGZULSSA-N 0.000 description 1
XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
230000029142 excretion Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
239000012467 final product Substances 0.000 description 1
229960004783 fotemustine Drugs 0.000 description 1
YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
201000010536 head and neck cancer Diseases 0.000 description 1
208000014829 head and neck neoplasm Diseases 0.000 description 1
UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
229960001101 ifosfamide Drugs 0.000 description 1
HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
238000009169 immunotherapy Methods 0.000 description 1
DBIGHPPNXATHOF-UHFFFAOYSA-N improsulfan Chemical compound CS(=O)(=O)OCCCNCCCOS(C)(=O)=O DBIGHPPNXATHOF-UHFFFAOYSA-N 0.000 description 1
229950008097 improsulfan Drugs 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
230000003902 lesion Effects 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
230000003908 liver function Effects 0.000 description 1
229960002247 lomustine Drugs 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
238000002595 magnetic resonance imaging Methods 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
229960001924 melphalan Drugs 0.000 description 1
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
206010061289 metastatic neoplasm Diseases 0.000 description 1
QTFKTBRIGWJQQL-UHFFFAOYSA-N meturedepa Chemical compound C1C(C)(C)N1P(=O)(NC(=O)OCC)N1CC1(C)C QTFKTBRIGWJQQL-UHFFFAOYSA-N 0.000 description 1
229950009847 meturedepa Drugs 0.000 description 1
QXYYYPFGTSJXNS-UHFFFAOYSA-N mitozolomide Chemical compound N1=NN(CCCl)C(=O)N2C1=C(C(=O)N)N=C2 QXYYYPFGTSJXNS-UHFFFAOYSA-N 0.000 description 1
229950005967 mitozolomide Drugs 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
235000010460 mustard Nutrition 0.000 description 1
230000008693 nausea Effects 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
229960001420 nimustine Drugs 0.000 description 1
VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 description 1
208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
238000011474 orchiectomy Methods 0.000 description 1
125000000962 organic group Chemical group 0.000 description 1
229960001592 paclitaxel Drugs 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
NUKCGLDCWQXYOQ-UHFFFAOYSA-N piposulfan Chemical compound CS(=O)(=O)OCCC(=O)N1CCN(C(=O)CCOS(C)(=O)=O)CC1 NUKCGLDCWQXYOQ-UHFFFAOYSA-N 0.000 description 1
229950001100 piposulfan Drugs 0.000 description 1
229960004694 prednimustine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
201000005825 prostate adenocarcinoma Diseases 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
229960002185 ranimustine Drugs 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
208000000587 small cell lung carcinoma Diseases 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000007940 sugar coated tablet Substances 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
229940061353 temodar Drugs 0.000 description 1
238000010998 test method Methods 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000003325 tomography Methods 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 1
229950001353 tretamine Drugs 0.000 description 1
229960000875 trofosfamide Drugs 0.000 description 1
UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
229960001055 uracil mustard Drugs 0.000 description 1
229940045136 urea Drugs 0.000 description 1
SPDZFJLQFWSJGA-UHFFFAOYSA-N uredepa Chemical compound C1CN1P(=O)(NC(=O)OCC)N1CC1 SPDZFJLQFWSJGA-UHFFFAOYSA-N 0.000 description 1
229950006929 uredepa Drugs 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Epidemiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Oncology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Silicon Polymers (AREA)

JP2003574174A 2002-03-08 2003-03-07 エポチロン誘導体およびアルキル化剤を含む組合せ剤 Withdrawn JP2005522461A (ja)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US36273802P	2002-03-08	2002-03-08
PCT/EP2003/002364 WO2003075899A2 (en)	2002-03-08	2003-03-07	Combinations comprising epothilone derivatives and alkylating agents

Publications (1)

Publication Number	Publication Date
JP2005522461A true JP2005522461A (ja)	2005-07-28

Family

ID=27805222

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP2003574174A Withdrawn JP2005522461A (ja)	2002-03-08	2003-03-07	エポチロン誘導体およびアルキル化剤を含む組合せ剤

Country Status (22)

Country	Link
EP (1)	EP1485090B1 (da)
JP (1)	JP2005522461A (da)
KR (1)	KR20040101274A (da)
CN (2)	CN1939299A (da)
AT (1)	ATE375157T1 (da)
AU (1)	AU2003223958B2 (da)
BR (1)	BR0308258A (da)
CA (1)	CA2478223C (da)
CY (1)	CY1107126T1 (da)
DE (1)	DE60316775T2 (da)
DK (1)	DK1485090T3 (da)
ES (1)	ES2295575T3 (da)
HU (1)	HUP0500092A2 (da)
IL (3)	IL163774A0 (da)
MX (1)	MXPA04008707A (da)
NO (1)	NO20044208L (da)
NZ (1)	NZ535081A (da)
PL (1)	PL371098A1 (da)
PT (1)	PT1485090E (da)
RU (1)	RU2341260C2 (da)
WO (1)	WO2003075899A2 (da)
ZA (1)	ZA200406790B (da)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2010525042A (ja) *	2007-04-25	2010-07-22	サイクラセルリミテッド	増殖性疾患を治療するためのサパシタビンの使用

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1999001124A1 (en)	1996-12-03	1999-01-14	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto, analogues and uses thereof
AU2011255647A1 (en)	2010-05-18	2012-11-15	Cerulean Pharma Inc.	Compositions and methods for treatment of autoimmune and other diseases

Citations (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1999042578A2 (en) *	1998-01-30	1999-08-26	Cold Spring Harbor Laboratory	Modulation of cell proliferation, methods and reagents
WO2000050423A1 (en) *	1999-02-22	2000-08-31	Gesellschaft Fuer Biotechnologische Forschung Mbh (Gbf)	C-21 modified epothilones
WO2000071521A1 (en) *	1999-05-21	2000-11-30	Bristol-Myers Squibb Co.	A process for the reduction of oxiranyl epothilones to olefinic epothilones
WO2002014323A2 (en) *	2000-08-16	2002-02-21	Bristol-Myers Squibb Company	Polymorphs of an epothilone analog

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6515016B2 (en) *	1996-12-02	2003-02-04	Angiotech Pharmaceuticals, Inc.	Composition and methods of paclitaxel for treating psoriasis
PT975638E (pt) *	1997-02-25	2002-12-31	Biotechnolog Forschung Mbh Gbf	Epothilons modificados nas cadeias laterais

2003
- 2003-03-07 EP EP03720323A patent/EP1485090B1/en not_active Expired - Lifetime
- 2003-03-07 CN CNA2006100879160A patent/CN1939299A/zh active Pending
- 2003-03-07 MX MXPA04008707A patent/MXPA04008707A/es active IP Right Grant
- 2003-03-07 IL IL16377403A patent/IL163774A0/xx unknown
- 2003-03-07 KR KR10-2004-7014013A patent/KR20040101274A/ko not_active Ceased
- 2003-03-07 NZ NZ535081A patent/NZ535081A/en not_active IP Right Cessation
- 2003-03-07 BR BR0308258-0A patent/BR0308258A/pt not_active IP Right Cessation
- 2003-03-07 DE DE60316775T patent/DE60316775T2/de not_active Expired - Lifetime
- 2003-03-07 AU AU2003223958A patent/AU2003223958B2/en not_active Ceased
- 2003-03-07 PL PL03371098A patent/PL371098A1/xx not_active Application Discontinuation
- 2003-03-07 HU HU0500092A patent/HUP0500092A2/hu unknown
- 2003-03-07 CA CA2478223A patent/CA2478223C/en not_active Expired - Fee Related
- 2003-03-07 CN CNB038055309A patent/CN100402029C/zh not_active Expired - Fee Related
- 2003-03-07 PT PT03720323T patent/PT1485090E/pt unknown
- 2003-03-07 DK DK03720323T patent/DK1485090T3/da active
- 2003-03-07 ES ES03720323T patent/ES2295575T3/es not_active Expired - Lifetime
- 2003-03-07 RU RU2004130283/15A patent/RU2341260C2/ru not_active IP Right Cessation
- 2003-03-07 JP JP2003574174A patent/JP2005522461A/ja not_active Withdrawn
- 2003-03-07 AT AT03720323T patent/ATE375157T1/de active
- 2003-03-07 WO PCT/EP2003/002364 patent/WO2003075899A2/en not_active Ceased
2004
- 2004-08-26 IL IL163774A patent/IL163774A/en not_active IP Right Cessation
- 2004-08-26 ZA ZA200406790A patent/ZA200406790B/en unknown
- 2004-10-04 NO NO20044208A patent/NO20044208L/no not_active Application Discontinuation
2008
- 2008-01-03 CY CY20081100012T patent/CY1107126T1/el unknown
- 2008-01-17 IL IL188859A patent/IL188859A0/en unknown

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1999042578A2 (en) *	1998-01-30	1999-08-26	Cold Spring Harbor Laboratory	Modulation of cell proliferation, methods and reagents
JP2003518359A (ja) *	1998-01-30	2003-06-10	コールドスプリングハーバーラボラトリー	細胞増殖の調節、方法および試薬
WO2000050423A1 (en) *	1999-02-22	2000-08-31	Gesellschaft Fuer Biotechnologische Forschung Mbh (Gbf)	C-21 modified epothilones
JP2002537395A (ja) *	1999-02-22	2002-11-05	ゲゼルシヤフト・フユア・ビオテヒノロギツシエ・フオルシユング・ミツト・ベシユレンクテル・ハフツング・（ゲーベーエフ）	Ｃ−２１変性エポチロン化合物
WO2000071521A1 (en) *	1999-05-21	2000-11-30	Bristol-Myers Squibb Co.	A process for the reduction of oxiranyl epothilones to olefinic epothilones
JP2003500394A (ja) *	1999-05-21	2003-01-07	ブリストル−マイヤーズスクイブカンパニー	オキシラニルエポチロン化合物のオレフィン性エポチロン化合物への還元法
WO2002014323A2 (en) *	2000-08-16	2002-02-21	Bristol-Myers Squibb Company	Polymorphs of an epothilone analog
JP2004506638A (ja) *	2000-08-16	2004-03-04	ブリストル−マイヤーズ　スクイブ　カンパニー	エポチロンアナログの多形

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2010525042A (ja) *	2007-04-25	2010-07-22	サイクラセルリミテッド	増殖性疾患を治療するためのサパシタビンの使用
JP2015013877A (ja) *	2007-04-25	2015-01-22	サイクラセルリミテッド	増殖性疾患を治療するためのサパシタビンの使用
US9675631B2 (en)	2007-04-25	2017-06-13	Cyclacel Limited	Dosing regimens for treatment of proliferative disorders comprising administration of sapacitabine

Also Published As

Publication number	Publication date
NZ535081A (en)	2007-05-31
EP1485090A2 (en)	2004-12-15
HUP0500092A2 (hu)	2005-04-28
DE60316775D1 (de)	2007-11-22
EP1485090B1 (en)	2007-10-10
ATE375157T1 (de)	2007-10-15
IL163774A0 (en)	2005-12-18
BR0308258A (pt)	2005-01-04
AU2003223958B2 (en)	2007-04-19
CN1939299A (zh)	2007-04-04
KR20040101274A (ko)	2004-12-02
IL163774A (en)	2010-12-30
AU2003223958A1 (en)	2003-09-22
CN100402029C (zh)	2008-07-16
CN1638767A (zh)	2005-07-13
ES2295575T3 (es)	2008-04-16
NO20044208D0 (no)	2004-10-04
NO20044208L (no)	2004-10-14
WO2003075899A2 (en)	2003-09-18
CA2478223C (en)	2012-05-15
HK1072723A1 (en)	2005-09-09
ZA200406790B (en)	2006-05-31
PL371098A1 (en)	2005-06-13
RU2341260C2 (ru)	2008-12-20
IL188859A0 (en)	2008-04-13
WO2003075899A3 (en)	2004-03-11
DE60316775T2 (de)	2008-04-30
MXPA04008707A (es)	2006-03-08
DK1485090T3 (da)	2008-02-04
PT1485090E (pt)	2008-01-14
CA2478223A1 (en)	2003-09-18
RU2004130283A (ru)	2005-08-10
CY1107126T1 (el)	2012-10-24

Legal Events

Date	Code	Title	Description
2006-03-08	A621	Written request for application examination	Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060307
2009-08-05	A131	Notification of reasons for refusal	Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090804
2009-11-05	A521	Request for written amendment filed	Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091104
2009-11-26	A521	Request for written amendment filed	Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20091104
2009-12-02	A02	Decision of refusal	Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20091201
2010-04-01	A521	Request for written amendment filed	Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100331
2010-04-23	A911	Transfer to examiner for re-examination before appeal (zenchi)	Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20100422
2010-10-04	A912	Re-examination (zenchi) completed and case transferred to appeal board	Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20101001
2011-11-03	A761	Written withdrawal of application	Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20111102

Publication	Publication Date	Title
US20090246172A1 (en)	2009-10-01	Compositions comprising epothilones and their use for the treatment of carcinoid syndrome
EP4447973A1 (en)	2024-10-23	Use of combination therapy for treating cancer
JP2005522461A (ja)	2005-07-28	エポチロン誘導体およびアルキル化剤を含む組合せ剤
CA2501610C (en)	2012-01-03	Epothilone derivatives for the treatment of multiple myeloma
EP1854464A2 (en)	2007-11-14	Combinations comprising epothilone derivatives
AU2007201437A1 (en)	2007-04-19	Combinations comprising epothilone derivatives and alkylating agents
US7754716B2 (en)	2010-07-13	Combination comprising a vasculostatic compound and an alkylating agent for the treatment of a tumor
HK1072723B (en)	2008-03-28	Combinations comprising an epothilone derivatives and an imidazotetrazinone
AU2002366531B2 (en)	2007-02-22	Compositions comprising epothilones and their use for the treatment of carcinoid syndrome
ZA200404013B (en)	2005-08-29	Compositions comprising epothilones and their use for the treatment of carcinoid syndrome.
HK1069983B (en)	2007-01-19	Compositions comprising epothilones and their use for the treatment of the carcinoid syndrome
TW201032798A (en)	2010-09-16	Antitumor combination combining AVE8062 and docetaxel